{"doi":"10.1016/j.omton.2025.201109","title":"Repurposing the SSRI paroxetine increases lymphocyte mobilization and improves the efficacy of measles virus-based immunovirotherapy","abstract":"Glioblastoma (GBM) is the most common primary malignant brain tumor, with a poor prognosis and limited response to immunotherapy. Systemic immunosuppression in GBM is a significant challenge partly driven by T cell sequestration in the bone marrow via sphingosine-1-phosphate receptor 1 (S1P1) internalization by G protein-coupled receptor kinase 2 (GRK-2). We demonstrated that immunovirotherapy based on oncolytic measles virus armed with the neutrophil-activating protein (MV-s-NAP), combined with anti-PD-1 and anti-TIGIT, increases S1P1 expression on bone marrow lymphocytes. Furthermore, repurposing paroxetine, one of the Food and Drug Administration-approved selective serotonin reuptake inhibitors (SSRIs) with GRK-2 inhibitory action, enhanced this effect, leading to greater lymphocyte circulation, activation, and improved survival in an orthotopic syngeneic mouse model. By overcoming key mechanisms of immune suppression and repurposing a widely available, clinically safe drug, this strategy represents a highly translatable approach to enhancing the efficacy of immunovirotherapy for gliomas.","journal":"Molecular Therapy Oncology","year":2025,"id":586247,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":395867,"name":"Susanna C. Concilio","orcid":"0000-0001-6950-2146","position":1,"is_corresponding":false},{"id":1500771,"name":"Kim B. Viker","orcid":null,"position":2,"is_corresponding":false},{"id":1500772,"name":"Susan M. Clark","orcid":null,"position":3,"is_corresponding":false},{"id":347148,"name":"Steven I. Robinson","orcid":"0000-0002-1648-1908","position":4,"is_corresponding":false},{"id":247463,"name":"Evanthia Galanis","orcid":"0000-0001-8014-786X","position":5,"is_corresponding":false},{"id":1500770,"name":"Georgios M. Stergiopoulos","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:59:28.666390Z","pmid":"41542034","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}